Cumulative oxytocin dose in spontaneous labour - Adverse postpartum outcomes, childbirth experience, and breastfeeding.

OBJECTIVES: This study aimed to determine the association between the total cumulative oxytocin dose during labour and adverse postpartum outcomes, childbirth experience and breastfeeding in term primiparous women with spontaneous onset of labour. STUDY DESIGN: A prospective observational multicentre study, including 1395 women with spontaneous labour, in seven hospitals in Southeast Sweden. Multivariable logistic regression (Crude Odds Ratios (OR) and adjusted OR (aOR) for relevant confounders) was used to analyze the association between oxytocin dose and postpartum outcomes. The exposure was the cumulative oxytocin dose during labour, classified in percentiles (<25th, 25-75th, >75th). The outcomes were occurrence of obstetric anal sphincter injury, postpartum haemorrhage (blood loss > 1000 ml), Apgar score < 7 at five minutes, umbilical cord arterial pH, postpartum bladder overdistension, exclusive breastfeeding at one week and three months, and the woman's perceived birth experience. RESULTS: Women receiving high amounts (>75th percentile, >4370 mU) of oxytocin infusion during labour had an increased risk of postpartum haemorrhage (OR 2.73 (1.78-4.19)), an overdistended bladder (OR 2.19 (1.11-4.31)), an infant with an Apgar score < 7 at five minutes (OR 2.89 (1.27-6.57)), a negative birth experience (OR 1.83 (1.25-2.69)), and a decreased chance of exclusive breastfeeding at one week (OR 0.63 (0.41-0.96)). After adjusting for confounders, all outcomes remained statistically significant except risk of low Apgar score and chance of exclusive breastfeeding. CONCLUSION: In women with high cumulative oxytocin dose during labour prompt, and prophylactic administration of uterotonics after delivery of the placenta should be considered to reduce the risk of postpartum haemorrhage. The risk for bladder overdistension can be reduced by implementing routines for observation for signs of bladder filling in the early postpartum period, as well as routine use of bladder scans post micturition to assess for successful bladder emptying. As women's birth experience have a major impact on their future mental health, should be routinely assessed postpartum, and support should be offered to women with negative experiences.

Assessing the effects of oxytocin in changes of core body temperature during LPS-induced endotoxemia: A novel approach using Extended Poincaré Plot Analysis.

Oxytocin has shown cardioprotective effects during inflammation and may modify the core body temperature changes in LPS-induced endotoxemia. Notably, the time series analysis of core body temperature fluctuations may indicate thermoregulation alterations. This study aims to assess the effects of oxytocin on changes in the core body temperature by analyzing the fluctuations of the temperature time series of endotoxemic rats. Twelve hours of continuous core body temperature fluctuations time series were obtained from adult male Dark Agouti rats implanted with a telemetric transmitter under the following treatment: lipopolysaccharide (LPS); oxytocin (O); lipopolysaccharide + oxytocin (LPS + O), and vehicle or control (C). The temperature fluctuations time series were analyzed using the Extended Poincaré Plot Analysis (EPPA), a novel approach for measuring nonlinear features, to compute the autocorrelation by Pearson's correlation coefficient r, the standard deviation perpendicular to the line of identity (SD1), and the standard deviation parallel to the line of identity (SD2). The autocorrelation of the temperature fluctuations assessed by Pearson's coefficient was significantly higher in the LPS group compared to control rats (C). Likewise, the co-administration of oxytocin during endotoxemia (LPS + O) significantly reduced the autocorrelation and increased the short-term variability (SD1) of temperature fluctuations compared to those recorded with a single dose of LPS. Thus, we concluded that oxytocin may introduce thermoregulatory changes under LPS-induced endotoxemia. The EPPA is a simple and powerful approach to assess physiological variability that can provide valuable insights into changes in thermoregulation.

Oxytocin is not associated with postpartum hemorrhage in labor augmentation in a retrospective cohort study in the United States.

BACKGROUND: Previous studies reported conflicting results on the relationship between oxytocin use for labor augmentation and the risk of postpartum hemorrhage, probably because it is rather challenging to disentangle oxytocin use from labor dystocia. OBJECTIVE: This study aimed to investigate the independent association between oxytocin use for augmentation and the risk of postpartum hemorrhage by using advanced statistical modeling to control for labor patterns and other covariates. STUDY DESIGN: We used data from 20,899 term, cephalic, singleton pregnancies of patients with spontaneous onset of labor and no previous cesarean delivery from Intermountain Healthcare in Utah in the Consortium on Safe Labor. Presence of postpartum hemorrhage was identified on the basis of a clinical diagnosis. Propensity scores were calculated using a generalized linear mixed model for oxytocin use for augmentation, and covariate balancing generalized propensity score was applied to obtain propensity scores for the duration and total dosage of oxytocin augmentation. A weighted generalized additive mixed model was used to depict dose-response curves between the duration and total dosage of oxytocin augmentation and the outcomes. The average treatment effects of oxytocin use for augmentation on postpartum hemorrhage and estimated blood loss (mL) were assessed by inverse probability weighting of propensity scores. RESULTS: The odds of both postpartum hemorrhage and estimated blood loss increased modestly when the duration and/or total dosage of oxytocin used for augmentation increased. However, in comparison with women for whom oxytocin was not used, oxytocin augmentation was not clinically or statistically significantly associated with estimated blood loss (6.5 mL; 95% confidence interval, 2.5-10.3) or postpartum hemorrhage (adjusted odds ratio, 1.02; 95% confidence interval, 0.82-1.24) when rigorously controlling for labor pattern and potential confounders. The results remained consistent regardless of inclusion of women with an intrapartum cesarean delivery. CONCLUSION: The odds of postpartum hemorrhage and estimated blood loss increased modestly with increasing duration and total dosage of oxytocin augmentation. However, in comparison with women for whom oxytocin was not used and after controlling for potential confounders, there was no clinically significant association between oxytocin use for augmentation and estimated blood loss or the risk of postpartum hemorrhage.

Association between duration of intrapartum oxytocin exposure and obstetric hemorrhage.

PURPOSE: Prolonged duration of intrapartum oxytocin exposure is included as a risk factor within widely adopted obstetric hemorrhage risk stratification tools. However, the duration of exposure that confers increased risk is poorly understood. This study aimed to assess the association between duration of intrapartum oxytocin exposure and obstetric blood loss, as measured by quantitative blood loss, and hemorrhage-related maternal morbidity. METHODS: This was a retrospective cohort study of all deliveries from 2018 to 2019 at a single medical center. We included patients who had received any intrapartum oxytocin, and we categorized them into 1 of 5 groups: > 0-2, ≥ 2-4, ≥ 4-6, ≥ 6-12, and ≥ 12 h of intrapartum oxytocin exposure. The primary outcomes were mean quantitative blood loss, proportion with obstetric hemorrhage (defined as quantitative blood loss ≥ 1000 mL), and proportion with obstetric hemorrhage-related morbidity, a composite of hemorrhage-related morbidity outcomes. Secondary outcomes were hemorrhage-related pharmacologic and procedural interventions. A stratified analysis was also conducted to examine primary and secondary outcomes by delivery mode. RESULTS: Of 5332 deliveries between January 1, 2018 and December 31, 2019 at our institution, 2232 (41.9%) utilized oxytocin for induction or augmentation. 326 (14.6%) had exposure of > 0-2 h, 295 (13.2%) ≥ 2-4 h, 298 (13.4%) ≥ 4-6 h, 562 (25.2%) ≥ 6-12 h, and 751 (33.6%) ≥ 12 h. Across all deliveries, there was higher mean quantitative blood loss (p < 0.01) as well as increased odds of obstetric hemorrhage (adjusted odds ratio [aOR] 1.52, 95% confidence interval [CI] 1.21-1.91) for those with ≥ 12 h of oxytocin compared to all groups between > 0-12 h of exposure. In our stratified analysis, ≥ 12 h of oxytocin exposure was associated with higher mean quantitative blood loss (p = 0.04) and odds of obstetric hemorrhage in vaginal deliveries (aOR 1.47, 95% CI: 1.03-2.11), though not in cesarean deliveries (aOR 1.16, 95% CI 0.82-1.62). There were no differences in proportion with obstetric hemorrhage-related morbidity across all deliveries (p = 0.40) or in the stratified analysis. CONCLUSION: Intrapartum oxytocin exposure of ≥ 12 h was associated with increased quantitative blood loss and odds of obstetric hemorrhage in vaginal, but not cesarean, deliveries.

Induction of labor and risk of postpartum hemorrhage in women with vaginal delivery: A propensity score analysis.

OBJECTIVE: To explore the association between induction of labor (IOL) and postpartum hemorrhage (PPH) after vaginal delivery. METHODS: We included women from the merged database of three randomized prospective trials (TRACOR, CYTOCINON, and TRAAP) that measured postpartum blood loss precisely, with standardized methods. IOL was considered overall and according to its method. The association between IOL and PPH was tested by multivariate logistic regression modeling, adjusted for confounders, and by propensity score matching. The role of potential intermediate factors, i.e. estimated quantity of oxytocin administered during labor and operative vaginal delivery, was assessed with structural equation modeling. RESULTS: Labor was induced for 1809 of the 9209 (19.6%) women. IOL was associated with a significantly higher risk of PPH of 500 mL or more (adjusted odds ratio 1.56, 95% confidence interval 1.42-1.70) and PPH of 1000 mL or more (adjusted odds ratio 1.51, 95% confidence interval 1.16-1.96). The risk of PPH increased similarly regardless of the method of induction. The results were similar after propensity score matching (odds ratio for PPH ≥500 mL 1.57, 95% confidence interval 1.33-1.87, odds ratio for PPH ≥1000 mL 1.57, 95% confidence interval 1.06-2.07). Structural equation modeling showed that 34% of this association was mediated by the quantity of oxytocin administered during labor and 1.3% by women who underwent operative vaginal delivery. CONCLUSION: Among women with vaginal delivery, the risk of PPH is higher in those with IOL, regardless of its method, and after accounting for indication bias. The quantity of oxytocin administered during labor may explain one third of this association.

Carvacrol-Loaded Nanoemulsion Promotes Tocolytic and Anti-Dysmenorrhea Effects in Rodents.

INTRODUCTION: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities. METHOD: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV). RESULTS: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes. CONCLUSIONS: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

Effects of oxytocin induction on early postpartum hemorrhage, perineal integrity, and breastfeeding: a case-control study.

OBJECTIVE: The aim of this study was to evaluate the postpartum hemorrhage, perineal integrity, and breastfeeding results of mothers who underwent oxytocin induction in the first stage of labor in the early postpartum period. METHODS: This single-center observational case-control study was conducted in the obstetric unit of a public hospital in Istanbul. The study sampling included 44 pregnant women who received oxytocin induction (case group) and 44 pregnant women who did not receive oxytocin (control group). The Personal Information Form, LATCH Breastfeeding Assessment Tool, Breastfeeding Self-Efficacy Scale, Redness, Edema, Ecchymosis, Discharge, and Approximation Scale, and Postpartum Hemorrhage Collection Bag were used in data collection, and pad follow-up was carried out. RESULTS: The amount of hemorrhage in the first 24 h of the postpartum period and the mean Redness, Edema, Ecchymosis, Discharge, and Approximation Scale score were significantly higher in the case group. While 47.7% of the oxytocin-induced women had 1st or 2nd, and 11.4% had 3rd or 4th degrees of lacerations, 20.5% of the control group had 1st or 2nd, and 2.3% had 3rd or 4th degrees of lacerations. There was no significant difference between the mean scores of the Breastfeeding Self-Efficacy Scale and LATCH Breastfeeding Assessment Tool in both groups. CONCLUSION: According to the study findings, it was determined that oxytocin induction administered in the first stage of labor increased hemorrhage and perineal trauma in the early postpartum period but did not affect the results of breastfeeding. CLINICAL TRIAL REGISTRATION NUMBER: NCT04441125.

Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial.

BACKGROUND: Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity. METHODS: STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091. FINDINGS: Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population. INTERPRETATION: Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin. FUNDING: French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.

Preoperative versus postoperative misoprostol use for prevention of blood loss during caesarean section in pregnant women at term: a multi-centre randomised controlled trial.

OBJECTIVE: Caesarean section is associated with higher blood loss than vaginal delivery. This study was performed to compare the safety and efficacy of preoperative versus postoperative rectal and sublingual misoprostol use for prevention of blood loss in women undergoing elective caesarean delivery. METHODS: Eligible patients in Southeast Nigeria were randomly classified into those that received 600 µg of preoperative rectal, postoperative rectal, preoperative sublingual, and postoperative sublingual misoprostol. All patients received 10 units of intravenous oxytocin immediately after delivery. Data were analysed with SPSS Version 23. RESULTS: Preoperative sublingual misoprostol use caused the highest postoperative packed cell volume, least change in the packed cell volume, and lowest intraoperative blood loss. Preoperative sublingual and rectal misoprostol use was associated with better haematological indices and maternal outcomes than postoperative use by these routes. However, preoperative sublingual and rectal use caused more maternal side effects than postoperative use by these routes. CONCLUSION: Preoperative sublingual misoprostol was associated with the most favourable haematological indices. Although preoperative sublingual and rectal misoprostol use caused more maternal side effects, these routes were associated with better haematological indices and maternal outcomes than postoperative sublingual and rectal misoprostol use.

Continuous vs intermittent induction of labor with oxytocin in nulliparous patients: a randomized controlled trial.

BACKGROUND: Oxytocin is considered the drug of choice for the induction of labor, although the optimal protocol and infusion duration remain to be determined. OBJECTIVE: This study aimed to assess whether the duration of oxytocin infusion increases 24-hour delivery rates and affects the length of time-to-delivery and patient's experience. STUDY DESIGN: A randomized controlled trial was performed at a single tertiary medical center, between January 1, 2020 and June 30, 2022. Nulliparous patients with a singleton pregnancy at a vertex presentation and a Bishop score ≥6 were randomly assigned to receive either continuous (16 hours, with a 4 hours pause in between infusions) or intermittent (8 hours, with a 4 hours pause in between infusions) oxytocin infusion, until delivery. In both groups, infusion was halted when signs of maternal or fetal compromise were observed. Randomization was conducted with a computer randomization sequence generation program. The primary outcome was delivery within 24 hours from the first oxytocin infusion and the secondary outcome included time-to-delivery, mode of delivery, and additional maternal and neonatal outcomes. Seventy-two patients per group were randomized to reach 80% statistical power with a 20% difference in the primary outcome according to previous studies. RESULTS: A total of 153 patients were randomized, 72 to the continuous oxytocin infusion group and 81 to the intermittent infusion group. The total oxytocin infusion time was similar between the groups. Patients in the continuous arm were more likely to deliver within 24 hours from oxytocin initiation (79.73% vs 62.96%, P<.05), and had a shorter oxytocin-to-delivery time interval, compared with patients receiving intermittent treatment (9.3±3.7 hours vs 21±11.7 hours, P<.001). Furthermore, time from ruptured membranes to delivery was shorter (9.3±3.7 hours vs 21±11.7 hours; P<.0001) and chorioamnionitis was less frequent (9.46% vs 21%; P<.05) in the continuous compared with the intermittent arm. Cesarean delivery rate was 20% in both groups (P=.226). There was no difference in postpartum hemorrhage, or adverse neonatal outcomes between the groups. Patients receiving continuous oxytocin infusion were more satisfied with the birthing experience. CONCLUSION: Continuous infusion of oxytocin for labor induction in nulliparous patients with a favorable cervix may be superior to intermittent oxytocin infusion, because it shortens time-to-delivery, decreases chorioamnionitis rate, and improves maternal satisfaction, without affecting adverse maternal or neonatal outcomes.

Misoprostol with balloon vs oxytocin with balloon in high-risk pregnancy induction: a randomized controlled trial.

BACKGROUND: Pregnancies at high risk for maternal, fetal, or placental complications often necessitate induction of labor in the late preterm or early term period for delivery. Limited data exist on the safest method of induction to use in this specific patient population. OBJECTIVE: This study aimed to compare the combination of oxytocin plus a Cook balloon vs misoprostol plus a Cook balloon for induction of labor in high-risk pregnancies. STUDY DESIGN: We conducted an open-label, randomized controlled trial at a single institution from July 2020 to May 2022. The study was approved by the institutional review board and registered with ClinicalTrials.gov (NCT04492072). Individuals with a high-risk pregnancy, at least ≥22 weeks' gestation, with a singleton in cephalic presentation, Bishop score ≤6, and intact membranes were offered enrollment. A high-risk pregnancy was defined as a pregnancy with any of the following complications: hypertensive disease of pregnancy, fetal growth restriction, oligohydramnios, suspected placental abruption requiring delivery, uncontrolled pregestational diabetes, or abnormal biophysical profile or nonstress test requiring delivery. The primary outcome was the rate of cesarean delivery. Secondary maternal outcomes included induction to delivery interval, number of vaginal deliveries within 24 hours, rates of uterine tachysystole, intraamniotic infection, operative vaginal delivery, and postpartum hemorrhage. Secondary fetal outcomes included fetal heart rate abnormalities, stillbirth, Apgar scores <7 at 5 minutes, admission to the neonatal intensive care unit, arterial umbilical blood pH <7.1, sepsis, and neonatal death. A subgroup analysis was planned for the primary outcome to assess the different indications for cesarean delivery. An intent-to-treat analysis was performed. RESULTS: During the 22 months of the trial, a total of 150 patients were randomized, and 73 (49%) of those were induced with oxytocin and a Cook balloon and 77 (51%) were induced with misoprostol and a Cook balloon. There was no significant difference in the overall rate of cesarean delivery between the study groups, (21.9% vs 31.1%; relative risk, 0.70; 95% confidence interval, 0.41-1.21), nor among those for which the cesarean delivery was performed for a specific indication. There were no differences in the secondary maternal and fetal or neonatal adverse outcomes. CONCLUSION: In high-risk pregnancies, the rate of cesarean delivery and adverse maternal and fetal outcomes were similar for induction of labor with oxytocin and a Cook balloon and for induction with misoprostol and a Cook balloon.

Term Delivery Complicated by Uterine Rupture with No Prior History of Cesarean Section or Uterine Curettage Following Oxytocin Use and Arrest in Second Stage of Labor: A Case Report.

BACKGROUND Uterine rupture during delivery in an unscarred uterus may be associated with oxytocin dose during second stage arrest and with underlying maternal factors. This report is of a 34-year-old woman, gravida 5, para 3, with no previous history of cesarean section (CS), who had a uterine rupture at term delivery following the use of oxytocin for second-stage arrest. CASE REPORT A 34-year-old Afghani woman, gravida 5, para 3 was admitted at term for delivery. The current pregnancy had been normal and the estimated birth weight was approximately 4000 g. There was no history of steroid treatment or any underlying connective tissue disease, and no history of dilation and curettage. Oxytocin was given as per protocol, starting at 20 ml/h of a dilution of 10 IU/1 L natrium chloride (NaCl). Subsequent labor progress was complicated by arrest of descent in the second stage of labor, necessitating cesarean section delivery. After opening the abdominal wall, a uterine rupture with several large blood clots was discovered, freely floating in the peritoneal space, about 500 ml in volume. The rupture stretched from the left side of the uterine body and down into the thin lower segment. The tissue in this area had diffuse hematoma. CONCLUSIONS Although uterine rupture mostly occurs in women with previous CS, this report has shown that uterine rupture can occur in pregnancy complicated by arrest in the second stage of labor.

Pharmacokinetics and safety of inhaled oxytocin compared with intramuscular oxytocin in women in the third stage of labour: A randomized open-label study.

AIMS: To compare pharmacokinetics (PK) and safety of heat-stable inhaled (IH) oxytocin with intramuscular (IM) oxytocin in women in third stage of labour (TSL), the primary endpoint being PK profiles of oxytocin IH and secondary endpoint of safety. METHODS: A phase 1, randomized, cross-over study was undertaken in 2 UK and 1 Australian centres. Subjects were recruited into 2 groups: Group 1, women in TSL; Group 2, nonpregnant women of childbearing potential (Cohort A, combined oral contraception; Cohort B, nonhormonal contraception). Participants were randomized 1:1 to: Group 1, oxytocin 10 IU (17 µg) IM or oxytocin 240 IU (400 µg) IH immediately after delivery; Group 2, oxytocin 5 IU (8.5 µg) intravenously and oxytocin 240 IU (400 µg) IH at 2 separate dosing sessions. RESULTS: Participants were recruited between 23 November 2016 to 4 March 2019. In Group 1, 17 participants were randomized; received either IH (n = 9) or IM (n = 8) oxytocin. After IH and IM administration, most plasma oxytocin concentrations were below quantification limits (2 pg/mL). In Group 2 (n = 14), oxytocin IH concentrations remained quantifiable ≤3 h postdose. Adverse events were reported in both groups, with no deaths reported: Group 1, IH n = 3 (33%) and IM n = 2 (25%); Group 2, n = 14 (100%). CONCLUSION: Safety profiles of oxytocin IH and IM were similar. However, PK profiles could not be established for oxytocin IH or IM in women in TSL, despite using a highly sensitive and specific assay.

Association of Labor Epidural Analgesia, Oxytocin Exposure, and Risk of Autism Spectrum Disorders in Children.

Importance: Maternal labor epidural analgesia (LEA) and oxytocin use for labor and delivery have been reported to be associated with child autism spectrum disorders (ASD). However, it remains unclear whether these 2 common medications used during labor and delivery have synergistic associations with ASD risk in children. Objective: To assess the independent associations of LEA and oxytocin during labor and delivery with ASD, as well as outcome modification associated with the concurrent use of both interventions. Design, Setting, and Participants: Data for this cohort study included 205 994 singleton births with vaginal deliveries in a single integrated health care system in Southern California from calendar years 2008 to 2017. Children were followed up to December 31, 2021. Data on use of LEA and oxytocin, covariates, and ASD outcome in children were obtained from electronic medical records. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) adjusting for covariates. Exposures: Labor epidural analgesia and/or oxytocin use during labor and delivery. Main Outcomes and Measures: A child's clinical diagnosis of ASD during follow-up and at age of diagnosis. Results: Among the cohort, 153 880 children (74.7%) were exposed to maternal LEA and 117 808 children (57.2%) were exposed to oxytocin during labor and delivery. The population of children was approximately half boys and half girls. The median (IQR) age of the mothers was 30.8 (26.8-34.5) years for those not exposed to LEA, 30.0 (25.9-33.8) years for those exposed to LEA, 30.4 (26.5-34.1) years for those unexposed to oxytocin, and 30.0 (25.9-33.9) years for those exposed to oxytocin during labor and delivery. A total of 5146 children (2.5%) had ASD diagnosed during follow-up. Oxytocin exposure was higher among LEA-exposed (67.7%) than -unexposed (26.1%) children. The ASD risk associated with LEA was independent of oxytocin exposure (HR, 1.28; 95% CI, 1.18-1.38); however, the ASD risk associated with oxytocin was not significant after adjusting for LEA exposure (HR, 1.05; 95% CI, 0.99-1.12). A significant interaction of LEA and oxytocin on child ASD risk was found (P = .02 for interaction). Compared with no exposure, HRs were 1.20 (95% CI, 1.09-1.32) for LEA alone, 1.30 (95% CI, 1.20-1.42) for both LEA and oxytocin, and 0.90 (95% CI, 0.78-1.04) for oxytocin alone. Conclusions and Relevance: The findings of this cohort study suggest an association between maternal LEA and ASD risk in children, and the risk appeared to be further increased if oxytocin was also administered. Oxytocin exposure without LEA exposure was not associated with ASD risk in children. These findings must be interpreted with caution. Further studies are needed to replicate or refute the study results and examine biological plausibility.

Uterine atony prophylaxis with carbetocin versus oxytocin and the risk of major haemorrhage during caesarean section: A retrospective cohort study.

Carbetocin and oxytocin are commonly recommended agents for active management of the third stage of labour. Evidence is inconclusive whether either one more effectively reduces the occurrence of important postpartum haemorrhage outcomes at caesarean section. We examined whether carbetocin is associated with a lower risk of severe postpartum haemorrhage (blood loss ≥ 1000 ml) in comparison with oxytocin for the third stage of labour in women undergoing caesarean section. This was a retrospective cohort study among women undergoing scheduled or intrapartum caesarean section between 1 January 2010 and 2 July 2015 who received carbetocin or oxytocin for the third stage of labour. The primary outcome was severe postpartum haemorrhage. Secondary outcomes included blood transfusion, interventions, third stage complications and estimated blood loss. Outcomes were examined overall and by timing of birth, scheduled versus intrapartum, using propensity score-matched analysis. Among 21,027 eligible participants, 10,564 women who received carbetocin and 3836 women who received oxytocin at caesarean section were included in the analysis. Carbetocin was associated with a lower risk of severe postpartum haemorrhage overall (2.1% versus 3.3%; odds ratio, 0.62; 95% confidence interval 0.48 to 0.79; P < 0.001). This reduction was apparent irrespective of timing of birth. Secondary outcomes also favoured carbetocin over oxytocin. In this retrospective cohort study, the risk of severe postpartum haemorrhage associated with carbetocin was lower than that associated with oxytocin in women undergoing caesarean section. Randomised clinical trials are needed to further investigate these findings.

Hypotension duration and vasopressor requirements following intrathecal oxytocin for Total hip arthroplasty: Secondary analysis of a randomized controlled trial.

INTRODUCTION: A recent publication investigating intrathecal oxytocin, 100 µg, administered immediately prior to a spinal anesthetic in patients undergoing primary total hip arthroplasty surgery demonstrated a reduction in disability for 3-weeks, increased walking distance at 8-weeks, and earlier opioid cessation. This secondary analysis study was undertaken to assess the acute cardiovascular safety and analgesic efficacy of intrathecal oxytocin in this study population. METHODS: 90 patients were included in the analysis (44 randomized to spinal oxytocin and 46 to placebo [saline]). Data collected prospectively during the previously published study were supplemented with additional retrospectively collected data. The primary outcomes were comparisons of the duration of hypotension (minutes with mean arterial pressure < 65 mmHg) and cumulative vasopressor requirements during the initial 60 min following spinal placement. Secondary outcomes included hypotension durations and vasopressor requirements at later time points, perioperative fluid administration, physical therapy metrics, time to first opioid administration, cumulative opioid consumption through 24 h, and verbal pain scores through 24 h. RESULTS: The duration of hypotension during the first 60 min following spinal placement did not differ between intrathecal oxytocin and placebo groups (12.2 ± 10.7 vs 14.0 ± 13.0 min, respectively; p = 0.476). There was also no difference in cumulative vasopressor requirements (1303 ± 883 vs 1156 ± 818 µg [phenylephrine equivalents]; p = 0.413) during that time period. No group differences were found for any of the investigated secondary outcomes. CONCLUSION: The administration of 100 µg of intrathecal oxytocin does not significantly impact the duration of hypotension or the need for vasopressor agents when given as a component of a spinal anesthetic. The oxytocin and placebo groups also did not differ in regards to physical therapy related metrics, time to first opioid administration, cumulative opioids at 24-h, or pain scores through 24-h. What is already known on this topic: Rapid intravenous oxytocin causes hypotension after cesarean delivery, but intrathecal oxytocin does not cause hypotension in healthy volunteers. WHAT THIS STUDY ADDS: Compared to saline control, intrathecal oxytocin, 100 µg did not increase the duration of hypotension or vasopressor requirements in patients during total hip arthroplasty. How this study might affect research, practice, or policy: Lack of hypotension from intrathecal oxytocin in this study supports future investigations to further explore its potential benefits, in terms of both analgesia and functional recovery following surgery.